1. Field of the Invention
The present invention concerns new flexible sachets for transporting bio-pharmaceutical fluid products and a method of manufacturing them.
2. Description of the Prior Art
U.S. Pat. No. 5,350,080 describes sachets which can be used for cellular culture media and their rigid transportation container.
The bio-pharmaceuticals industry, understood in the broadest sense, is increasingly using flexible sachets with capacities in the range 20 liters to 2 000 liters and more, in particular bio-compatible sachets, to transport fluids use in the industry, such as culture media, cellular cultures, buffer solutions, artificial nutrient liquids, blood products or derived products such as plasma.
Sometimes the products contained in such sachets are used thousands of kilometers from the place where the sachets were filled. These products are often extremely valuable in financial terms and often extremely valuable in terms of the health of persons because they can be used to manufacture medication for human use, for example. It is therefore essential for such sachets to reach their destination safely, filled with the liquid with which they were initially filled, and free of contamination.
Flexible sachets of the above kind are subject to many kinds of stress during transportation: acceleration, braking, tossing, shaking, vibration, etc and therefore to many forces including shear forces which tend to deteriorate the film from which they are made, especially at sensitive locations such as folds. Consequently these various stresses frequently lead to weakening, rupture or piercing of the sachets.
It must be remembered that sachets of the above kind intended to contain the previously mentioned liquid products and media are by their very nature provided with a number of access ports enabling their content to be filled, drawn off, mixed, etc, for example, and usually with a number of tubes installed at some or all of these access ports. The tubes are themselves often fitted with one or more rigid material devices such as valves, filters or clamps which can contribute to abrasion of the upper part of the sachets when they are transported over long distances. A hole in the top of a sachet can be just as serious as one elsewhere, for example in the situation of transporting sterile contents.
This is why it would therefore be desirable to have a sachet for transporting bio-pharmaceutical liquids with a volume of 50 liters or more which in addition to the usual qualities of such sachets, i.e. biocompatibility, sterilizability, impermeability to gases and in particular to oxygen, would be particularly resistant to transportation over long distances and easy to manufacture.
Sachets for transporting bio-pharmaceutical liquids in the form of bellows with walls constructed by manually welding three separate independent films are known in themselves.
Sachets of the above type are sold by HyClone Laboratories, for example. They have capacities in the range 1 liter to 1 000 liters, for example. However, when transported over long distances, given the many stresses to which the sachets are subjected, a number of them are lost because of leaks.
This is why the subject matter of the present application is a flexible sachet for transporting bio-pharmaceutical liquids with a volume of 50 liters or more, of the bellows type, assuming when filled a substantially parallelepiped shape, comprising a bottom wall, a top wall and four lateral walls, which is made of a single laminated film with three or more layers, and preferably made of four pieces of the said single laminated film, the innermost layer being a plastics material layer that can be heat welded and is biocompatible with the media transported.
The bio-pharmaceutical liquids transported can be culture media, cell cultures, buffer solutions, artificial nutrient liquids, blood products or derivatives such as plasma, for example.
The sachet of the invention is a bellows type sachet, i.e. one in which, when laid flat, two opposite sides of the sachet are folded inwards.
The expression "laminated single film" or "monofilm" means that the film from which the walls of the sachet are made appears to be a single film although in fact it is made from a plurality of layers of films of different kinds stuck together.
In accordance with the invention, the laminated single film comprises at least three layers and preferably four layers.
The inside layer is a layer of plastics material that can be heat welded and is biocompatible with the media transported. These plastics materials include polyolefins, for example, and preferably polyethylene (PE), especially low-density and in particular ultra-low-density polyethylene.
The thickness of this layer can be in the range 50 .mu.m to 200 .mu.m, for example, and in particular in the range 100 .mu.m to 200 .mu.m.
The intermediate layer constituting a barrier to gases such as oxygen, carbon dioxide or water vapor, is for example made of polyamide (nylon) 6, polyamide 8, polyamide 11, polyamide 12, polyamide 6--6, polyamide 6-10, polyamide -6 or polyamide 6/polyamide 6--6 copolymers. Mixtures of gas barrier polymer resins can also be used such as a mixture of polyamide or polyethylene and ethylene/vinyl alcohol copolymer (EVOH) in polyvinylidene chloride (PVDC). A plastics material that has been surface treated with aluminum oxide or silica can equally be used. Under preferred conditions of implementation, the gas barrier intermediate layer is made of an ethylene/vinyl alcohol copolymer.
The thickness of this layer can be in the range 6 .mu.m to 20 .mu.m, for example, and in particular in the range from 10 .mu.m to 20 .mu.m.
The external layer is preferably made from a plastics material that has an insulating effect vis a vis heat welding, for example polyolafin or polyamide resin and preferably polyester (PET) resin.
The thickness of this layer can be in the range 10 .mu.m to 30 .mu.m, for example, and in particular in the range 10 .mu.m to 20 .mu.m.
Under preferred conditions of implementation of the invention the laminated film includes a fourth layer which is advantageously between the external layer and the gas barrier intermediate layer, improving the mechanical strength of the laminated single film.
This second intermediate layer can be of polyolafin or PET, for example, and is preferably of polyamide, advantageously polyamide 6.
The adhesive used to attach the various layers together is preferably one of the adhesives conventionally used in the field of laminated polymer films. An epoxy adhesive is preferably used, in particular one of the polyurethane-polyester type.
The above polymers can be mixed with additives. For example, the polyethylene of the inner layer can have a slippery agent added to it such as erucylamide in a concentration of 600 ppm and/or a silicon oxide at a concentration of 2 000 ppm.
Under preferred conditions of implementation of the invention, the above sachet is made from four pieces of film by flat heat welding.
This parallelepiped shape can in particular be obtained by cutting the edges of the film at 30.degree. to 60.degree. and approximately 45.degree. relative to the vertical axis of the sachet.
By definition, the "bottom face" and the "top face" of the sachet are the faces of the sachet such that the welds cross over on these faces but are parallel to each other on the "lateral" faces of the sachet.
Under other preferred conditions of implementation of the invention, the above sachet has on its top face a preferably elongate flange for mounting connectors comprising one or more chimneys for fitting connectors which are preferably identical, and in particular aligned, comprising two substantially cylindrical concentric lips.
These chimneys can advantageously cooperate with connectors having a cylindrical end sized to be inserted between the lips of the chimney. Their number is preferably in the range 1 to 8, in particular 2 to 6, especially 3 to 5.
Under preferred conditions of implementation the connectors further comprise an outer skirt surrounding the outer lip of the access chimney.
The connectors can have any conventional configuration such as, for example, fittings for tubes such as, for example, fittings for small, medium or large diameter tubes, stoppers, right-angle connections, and these connectors, in particular those for right-angle connections, can themselves comprise a double-lip system similar to that of the chimneys for connectors, for example.
Under other preferred conditions of implementation of the invention the flange for mounting connectors is made of polyolefin resin and preferably of an ethylenevinyl acetate copolymer.
Under other preferred conditions of implementation of the invention the connectors are glued to the chimneys using a solvent or non-solvent glue.
The present invention also consists in a sachet of the above kind fitted with connectors installed on the above chimneys.
Under other preferred conditions of implementation of the invention all the materials used to construct the sachet of the invention and its accessories are capable of withstanding exposure to radiation and other known sterilization techniques.
Under other preferred conditions of implementation of the invention the flange for mounting connectors carrying the chimneys is heat welded to the sachets.
Under other preferred conditions of implementation of the invention the mounting flange has in its lower part, opposite the access chimneys, one or in particular several spaced protuberances constituting passages, for example semi-toroidal passages, which prevent the plate being pressed totally against the bottom of the sachet when it is emptied.
Under further preferred conditions of implementation of the invention the mounting flange has standardized chimneys enabling easy customization of the outlet accessories and valves (stopper, angled or straight outlet, variety of diameters, etc).
Under other preferred conditions of implementation of the invention the bottom face of the sachet is fitted with a bung, for example an evacuation or filling bung. The evacuation or filling bung can be mounted on the sachet in the same way as the above plate. Under preferred conditions of implementation of the invention the bung includes a 90.degree. outlet.
Under further preferred conditions of use of the invention the emptying bung is mounted on a base installed in such a manner that it projects outwardly of the bottom of the sachet. The projecting part of the bung is preferably of polygonal shape or of any other non-circular shape, such as elongate oval, triangular, square, hexagonal, etc. This particular shape allows good centering of the sachet when the latter is installed in a rigid container for transportation by cooperation with an orifice of complementary shape and corresponding located on the bottom of the container. Also, the corners of the sachet can fit closely into the corners of the container without risk of twisting of the sachet. The bung can at the same time constitute a point at which the sachet is anchored to the bottom of the container, which improves transport.
Under other preferred conditions of implementation, the pro-eminent base of the bung has a peripheral groove which can cooperate with a clip so that it can be clipped when it is fitted into the container for filling. In this way the original position of the sachet is preserved.
The present invention also consists in a method of manufacturing a sachet as defined hereinabove wherein a top film, a bottom film and two lateral films folded on themselves are paid out in such a manner as to bring the heat weldable plastics material layers into contact with each other and in a flat configuration, leaving a gap between the two lateral films, followed by heat welding of the sides two by two and of the top and bottom of the sachet.
Under preferred conditions of implementation of the invention the top and bottom welds of the sachet are K-welds, the branches of the K being inclined at approximately 45.degree. to the direction of movement of the pieces of multilayer monofilm, for example in the range 30.degree. to 60.degree., as in the examples hereinafter.
Under preferred conditions of implementation of the invention the heat welding is effected using heating bars. A single weld can be effected at a given location. However, one, two or in particular three successive welds are preferably effected. In the case of welds in a plurality of steps, the steps are preferably effected at different temperatures.
Under other preferred conditions of implementation of the invention the welds are effected with a width in the range 5 mm to 20 mm, preferably 5 mm to 15 mm and in particular 8 mm to 15 mm.
The other operations, such as cutting the films at the welds, are conventional.
It is therefore possible to proceed in a single step to a plurality of welding operations at the same level, given the presence of the external layer which has an insulating effect vis a vis heat welding. Thus only the internal layer are welded together.